The pathophysiology of myocardial ischemia and its relationship to atherosclerosis is incompletely understood. The traditional view that coronary stenoses precipitate myocardial ischemia by limiting increases in blood flow is now thought to be incomplete. Experimental and clinical evidence has accumulated that dynamic biological processes in atherosclerotic coronary stenoses and resistance vessels both play an active role in causing ischemia by intermittently interfering with coronary blood flow. Subsequently, endothelial dysfunction has been shown to play a central role in this abnormal constrictor response. However, to date, the mechanisms of endothelial dysfunction in causing ischemia and the relationship of this dysfunction to the stages of atherosclerosis are not fully understood. The objectives of this study are: 1. To examine the temporal and spatial relationship between the extent of atherosclerosis, especially in the early phases of the disease and the development of endothelial vasodilator dysfunction. 2. To investigate whether atherosclerosis in large epicardial arteries is associated with the impairment of the endothelium-dependent vasodilator function in human coronary resistance vessels resulting in disturbed regulation of coronary flow. 3. To study if superoxide dismutase can reverse the loss of endothelium-dependent vasodilation in vivo in the atherosclerotic epicardial and resistance vessels, suggesting that excessive generation of superoxide radicals impairs normal endothelial function. 4. To assess the ability of therapeutic interventions (aggressive cholesterol lowering) to reverse signs of endothelial dysfunction and improve vasomotor responses in the coronary arteries of patients. this project aims to redefine coronary atherosclerosis in functional, in addition to structural terms and to treat endothelial dysfunction with the associated abnormal vasomotion as an essential component of atherosclerosis in the clinical setting.